Pal Sukumar, Tatarenkova Olga V, de la Maza Luis M
Department of Pathology and Laboratory Medicine, Medical Sciences I, University of California, Irvine, Irvine, CA, USA.
Immunology. 2015 Nov;146(3):432-43. doi: 10.1111/imm.12520. Epub 2015 Oct 1.
C3H/HeN female mice were vaccinated with native Chlamydia muridarum major outer membrane protein (MOMP), using Montanide+CpG or Alum+CpG as adjuvants. Negative control groups were immunized with ovalbumin (OVA) and the same adjuvants. As positive control, mice were inoculated intranasally with live Chlamydia. Mice were challenged in the ovarian bursa with 10(5) C. muridarum inclusion forming units. Six weeks after the genital challenge the animals were caged with male mice and monitored for pregnancy. Mice vaccinated with MOMP+Montanide+CpG developed high levels of C. muridarum-specific antibodies, with a high IgG2a/IgG1 ratio and neutralizing titres. Animals immunized using Alum+CpG had low antibody levels. Cellular immune responses were significantly higher in mice vaccinated with MOMP and Montanide+CpG, but not with Alum+CpG, when compared with negative controls. Following the genital challenge, only 20% (4/20) of mice vaccinated with MOMP+CpG+Montanide had positive vaginal cultures whereas 100% (9/9) of mice immunized with MOMP+CpG+Alum had positive cultures. Of the positive control animals inoculated with live Chlamydia only 15% (3/20) had positive vaginal cultures. In contrast, 100% (20/20) of mice immunized with OVA+CpG+Montanide, or minimal essential medium, had positive cultures. Following mating, 80% (16/20) of mice vaccinated with MOMP+CpG+Montanide, and 85% (17/20) of animals inoculated intranasally with live C. muridarum carried embryos in both uterine horns. No protection against infertility was observed in mice immunized with MOMP and CpG+Alum or OVA. In conclusion, this is the first time that a subunit vaccine has been shown to elicit a protective immune response in the highly susceptible C3H/HeN strain of mice against an upper genital challenge.
将C3H/HeN雌性小鼠用天然鼠衣原体主要外膜蛋白（MOMP）进行疫苗接种，使用Montanide+CpG或Alum+CpG作为佐剂。阴性对照组用卵清蛋白（OVA）和相同佐剂进行免疫。作为阳性对照，小鼠经鼻内接种活的衣原体。用10(5)个鼠衣原体包涵体形成单位对小鼠的卵巢囊进行攻毒。生殖道攻毒六周后，将这些动物与雄性小鼠关在一起并监测其是否怀孕。用MOMP+Montanide+CpG接种的小鼠产生了高水平的鼠衣原体特异性抗体，具有高IgG2a/IgG1比值和中和效价。用Alum+CpG免疫的动物抗体水平较低。与阴性对照组相比，用MOMP和Montanide+CpG接种的小鼠的细胞免疫反应显著更高，但用Alum+CpG接种的小鼠则不然。生殖道攻毒后，用MOMP+CpG+Montanide接种的小鼠中只有20%（4/20）阴道培养呈阳性，而用MOMP+CpG+Alum免疫的小鼠中有100%（9/9）阴道培养呈阳性。在接种活衣原体的阳性对照动物中，只有15%（3/20）阴道培养呈阳性。相比之下，用OVA+CpG+Montanide或最低限度基本培养基免疫的小鼠中有100%（20/20）阴道培养呈阳性。交配后，用MOMP+CpG+Montanide接种的小鼠中有80%（16/20），经鼻内接种活鼠衣原体的动物中有85%（17/20）双侧子宫角都有胚胎。在用MOMP和CpG+Alum或OVA免疫的小鼠中未观察到对不育的保护作用。总之，这是首次证明亚单位疫苗能在高度易感的C3H/HeN小鼠品系中引发针对上生殖道攻毒的保护性免疫反应。
